Histone and chromatin cross-talk

Abstract

Chromatin is the physiologically relevant substrate for all genetic processes inside the nuclei of eukaryotic cells. Dynamic changes in the local and global organization of chromatin are emerging as key regulators of genomic function. Indeed, a multitude of signals from outside and inside the cell converges on this gigantic signaling platform. Numerous post-translational modifications of histones, the main protein components of chromatin, have been documented and analyzed in detail. These 'marks' appear to crucially mediate the functional activity of the genome in response to upstream signaling pathways. Different layers of cross-talk between several components of this complex regulatory system are emerging, and these epigenetic circuits are the focus of this review.

HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

“…Histone H1 is bound to linker DNA between nucleosomes. 1,2 Histones are subject to multiple post-translational modifications (PTMs), including acetylation, methylation, ubiquitylation, phosphorylation, and sumoylation. These PTMs determine open and closed chromatin conformations, which, in turn, regulate the differential access and recruitment of transcription factors and other regulatory chromatin-binding proteins to DNA.…”

A feat of metabolic proportions: Pdx1 orchestrates islet development and function in the maintenance of glucose homeostasis

“…In this regard, basic unit of chromatin is formed by the complex between DNA and histone proteins; the covalent modifications of the amino terminal tails of histone proteins (including acetylation and methylation of Lys residues) have been demonstrated to alter chromatin packaging, and hence directly affect rates of gene transcription [152]. Interestingly, although Pdx1 itself does not appear to have intrinsic abilility to either modify histones or directly alter chromatin structure, its depletion in β cell lines results in the loss of histone H3-Lys4 dimethylation (a mark of active, open chromatin) at the insulin gene.…”

Structural insights into human KAP1 PHD finger–bromodomain and its role in gene silencing

“…Chemical modifications of chromatin on the DNA (for example, methylation of cytosine) and DNA-packing histones (for example, acetylation, methylation, phosphorylation, ubiquitination and SUMOylation) are important in the epigenetic control of gene transcription in response to physiological and environmental stimuli [1][2][3] . An emerging model suggests that there is an 'epigenetic code' embedded within chromatin to signify regions of distinct nuclear activities, such as heterochromatin formation or transcriptional activation [4][5][6] .…”

“…A comprehensive mutation-based structure-function analysis correlating transcriptional repression, ubiquitin-conjugating enzyme 9 (UBC9) binding and SUMOylation shows that the PHD finger and the bromodomain of KAP1 cooperate as one functional unit to facilitate lysine SUMOylation, which is required for KAP1 co-repressor activity in gene silencing. These results demonstrate a previously unknown unified function for the tandem PHD finger-bromodomain as an intramolecular small ubiquitin-like modifier (SUMO) E3 ligase for transcriptional silencing.Chemical modifications of chromatin on the DNA (for example, methylation of cytosine) and DNA-packing histones (for example, acetylation, methylation, phosphorylation, ubiquitination and SUMOylation) are important in the epigenetic control of gene transcription in response to physiological and environmental stimuli [1][2][3] . An emerging model suggests that there is an 'epigenetic code' embedded within chromatin to signify regions of distinct nuclear activities, such as heterochromatin formation or transcriptional activation [4][5][6] .…”